Recently evidence has been accumulated indicating that intermediate epoxides are responsible for mutagenic, carcinogenic or cytotoxic effects of many aromatic or olefinic compounds. Epoxide hydrases transform such epoxides much less reactive dihydrodiols. The overall objective is to clarify the role of epoxide hydrases in drug metabolism and especially their involvement in the mechanism of chemical carcinogenesis. Two epoxide hydrases appear to be present in liver microsomes, one with a very broad substrate specificity and another which is fairly specific for benzene oxide and possible some other closely related epoxides. The immediate objective is to separate these two enzymes, study their properties, develop specific inhibitors, and assess the relative importance of the two enzymes for the degradation of intermediate carcinogenic arena oxides derived from polycyclic aromatic hydrocarbons and of hepatotoxic arene oxides derived from halobenzenes, develop specific activators or inducers and assess their potential utility in possibly even preventing chemical carcinogenesis or hepatotoxicity evoked by arene oxides.